chr9-128322877-C-T
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_016035.5(COQ4):c.19C>T(p.Pro7Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000489 in 1,431,334 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_016035.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COQ4 | NM_016035.5 | c.19C>T | p.Pro7Ser | missense_variant | 1/7 | ENST00000300452.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COQ4 | ENST00000300452.8 | c.19C>T | p.Pro7Ser | missense_variant | 1/7 | 1 | NM_016035.5 | P1 | |
COQ4 | ENST00000372875.3 | c.19C>T | p.Pro7Ser | missense_variant | 1/4 | 2 | |||
COQ4 | ENST00000608951.5 | c.19C>T | p.Pro7Ser | missense_variant | 1/3 | 2 | |||
COQ4 | ENST00000609948.1 | c.19C>T | p.Pro7Ser | missense_variant | 1/2 | 2 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome AF: 0.00000489 AC: 7AN: 1431334Hom.: 0 Cov.: 30 AF XY: 0.00000141 AC XY: 1AN XY: 710752
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Neonatal encephalomyopathy-cardiomyopathy-respiratory distress syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 03, 2021 | This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 7 of the COQ4 protein (p.Pro7Ser). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The serine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. This variant has not been reported in the literature in individuals affected with COQ4-related conditions. This variant is present in population databases (no rsID available, gnomAD no frequency). - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 07, 2021 | The c.19C>T (p.P7S) alteration is located in exon 1 (coding exon 1) of the COQ4 gene. This alteration results from a C to T substitution at nucleotide position 19, causing the proline (P) at amino acid position 7 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at